Perceptions of the impact of a multidose human-milk fortifier on human-milk preparation practices in United States neonatal intensive care units: A survey of nutrition care team members.

BACKGROUND: In 2020, a multidose human-milk fortifier (MDHMF) was designed to improve the process of human-milk (HM) fortification. The bottle of MDHMF (5.5 oz, 163 ml) allows aseptic removal of HMF in a precise measure. This survey aimed to examine the experience of nutrition care team (NCT) members who used the MDHMF in a hospital setting. METHODS: A survey link (Qualtrics XM) was sent to NCT leaders (N = 108) at hospitals who participated in an evaluation of the MDHMF from June 1, 2020, through April 30, 2021. The NCT leaders sent the survey to members at their prospective hospitals (n = 344). The investigators did not know the identities of the recipients of the survey and collected no identifying information on respondents. Respondents were asked to evaluate their experience with the MDHMF compared with their previous practice. RESULTS: The majority of respondents (n = 63, 72%) reported that the MDHMF improved their HM preparation practices and was better than their previous practice for reducing the time to prepare (n = 33, 71.7%), ensuring the accuracy of fortified HM (n = 32, 69.6%), ensuring aseptic preparation (n = 24, 52.2%), reducing HM waste (n = 27, 58.7%), and being easy to use (n = 30, 65.2%). Those responsible for evaluating nutrition status answered that the MDHMF was the same for feeding tolerance (n = 41, 58.6%), weight gain (n = 47, 67.1%), head growth (n = 56, 81.2%), and length growth (n = 53, 76.8%). CONCLUSION: US neonatal intensive care unit NCT members perceived that the MDHMF resulted in improved HM preparation practices while maintaining growth and tolerance.

Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. DESIGN: Longitudinal study. PARTICIPANTS: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017. MEASUREMENTS: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. RESULTS: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed. CONCLUSIONS: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

Mechanisms of Immunotherapy Resistance in Cutaneous Melanoma: Recognizing a Shapeshifter.

Melanoma is one of the seven most common cancers in the United States, and its incidence is still increasing. Since 2011, developments in targeted therapies and immunotherapies have been essential for significantly improving overall survival rates. Prior to the advent of targeted and immunotherapies, metastatic melanoma was considered a death sentence, with less than 5% of patients surviving more than 5 years. With the implementation of immunotherapies, approximately half of patients with metastatic melanoma now survive more than 5 years. Unfortunately, this also means that half of the patients with melanoma do not respond to current therapies and live less than 5 years after diagnosis. One major factor that contributes to lower response in this population is acquired or primary resistance to immunotherapies via tumor immune evasion. To improve the overall survival of melanoma patients new treatment strategies must be designed to minimize the risk of acquired resistance and overcome existing primary resistance. In recent years, many advances have been made in identifying and understanding the pathways that contribute to tumor immune evasion throughout the course of immunotherapy treatment. In addition, results from clinical trials focusing on treating patients with immunotherapy-resistant melanoma have reported some initial findings. In this review, we summarize important mechanisms that drive resistance to immunotherapies in patients with cutaneous melanoma. We have focused on tumor intrinsic characteristics of resistance, altered immune function, and systemic factors that contribute to immunotherapy resistance in melanoma. Exploring these pathways will hopefully yield novel strategies to prevent acquired resistance and overcome existing resistance to immunotherapy treatment in patients with cutaneous melanoma.

Symmetric dimethylarginine concentrations in healthy neonatal foals and mares.

BACKGROUND: Symmetric dimethylarginine (SDMA) is a renal biomarker correlated with glomerular filtration rate (GFR). OBJECTIVES: Describe changes in SDMA in clinically healthy foals and their mares during the first month postfoaling. ANIMALS: Convenience sampling of healthy periparturient Thoroughbred mares and their full-term foals from a population of client-owned horses. METHODS: Serum and EDTA whole blood samples were collected from mares in their last month of pregnancy and then from mares and foals at approximately <12 hours, 48 hours, 7 days, and 30 days postbirth. Samples were processed at a commercial reference laboratory for CBC and serum biochemistry, including SDMA concentrations. RESULTS: A total of 125 foals and 104 mares were included. Upper limits for SDMA concentrations in foals were above the adult horse reference interval for the first 20 or more days of life. Median SDMA concentrations decreased from 70 µg/dL (range, 7-100 µg/dL) to 18 µg/dL (range, 6-27 µg/dL) during the first 3 to 4 weeks of life. At birth, the SDMA concentration reference range was established as 0 to 100 µg/dL (upper limit of the assay); 0 to 85 µg/dL for 1 to 4 days old, 0 to 36 µg/dL for 5 to 10 days old, and 0 to 24 µg/dL for 20 to 30 days old. The upper reference limits for SDMA concentrations in mares did not differ from the general reference interval for adult horses. No correlation was identified between mare and foal SDMA concentrations (ρ = .06, P = .58). CONCLUSIONS AND CLINICAL IMPORTANCE: Foal SDMA concentrations remained higher than the upper limit of the adult reference range and foals require a different reference range dependent on age.

Screening for HIV-Associated Neurocognitive Disorder (HAND) in Adults Aged 50 and Over Attending a Government HIV Clinic in Kilimanjaro, Tanzania. Comparison of the International HIV Dementia Scale (IHDS) and IDEA Six Item Dementia Screen.

Validated screening tools for HIV-associated neurocognitive disorders (HAND) are lacking for the newly emergent ageing population of people living with HIV (PLWH) in sub-Saharan Africa (SSA). We aimed to validate and compare diagnostic accuracy of two cognitive screening tools, the International HIV dementia scale (IHDS), and the Identification and Interventions for Dementia in Elderly Africans (IDEA) screen, for identification of HAND in older PLWH in Tanzania. A systematic sample of 253 PLWH aged ≥ 50 attending a Government clinic in Tanzania were screened with the IHDS and IDEA. HAND were diagnosed by consensus American Academy of Neurology (AAN) criteria based on detailed clinical neuropsychological assessment. Strict blinding was maintained between screening and clinical evaluation. Both tools had limited diagnostic accuracy for HAND (area under the receiver operating characteristic (AUROC) curve 0.639-0.667 IHDS, 0.647-0.713 IDEA), which was highly-prevalent (47.0%). Accurate HAND screening tools for older PLWH in SSA are needed.

RESUMEN: Faltan pruebas cognitivas válidas para los trastornos neurocognitivos asociados al VIH (según sus siglas en inglés, HIV-Associated Neurocognitive Disorder (HAND) en la población emergente de personas mayores que viven con el VIH en el África subsahariana. Nuestro objetivo era validar y comparar la precisión diagnóstica de dos pruebas cognitivas, la escala internacional de demencia por VIH (según sus siglas en ingles International HIV dementia scale (IHDS) y la prueba 'IDEA', para el cribado de trastornos neurocognitivos asociados al VIH (HAND) en personas mayores viviendo con VIH en Tanzania. Una muestra sistemática de 253 personas de ≥50 años que asistieron a una clínica gubernamental en Tanzania se examinó con el IHDS y la IDEA. HAND fueron diagnosticados por consenso según los criterios de la Academia Americana de Neurología (AAN) basados en una detallada evaluación neuropsicológica y clínica. Las fases de cribado y de evaluación clínica se realizaron de forma independiente y a ciegas. Ambas herramientas tenían una precisión de diagnóstico limitada para HAND (área bajo la característica de funcionamiento del receptor (AUROC) curva 0.639 ­ 0.667 IHDS, 0.647-0.713 IDEA). HAND era altamente frecuente (47%). Se necesitan pruebas cognitivas por cribado de deterioro cognitivo en personas mayores con VIH en el África subsahariana.

The Relative Merits of an Individualized Versus a Generic Approach to Rating Functional Performance in Childhood Dystonia.

AIMS: The Performance Quality Rating Scale (PQRS) is an observational measure that captures performance at the level of activity and participation. Developed for use with the Cognitive Orientation to daily Occupational Performance (CO-OP), it is a highly individualized approach to measurement. CO-OP is currently being studied in childhood-onset hyperkinetic movement disorders (HMD) and deep brain stimulation. The purpose of this study was to compare two different approaches to rating performance, generic (PQRS-G) and individualized (PQRS-I), for children with childhood-onset hyperkinetic movement disorders (HMD) including dystonia. METHOD: Videotaped activity performances, pre and post intervention were independently scored by two blind raters using PQRS-G PQRS-I. Results were examined to determine if the measures identified differences in e performance on goals chosen by the participants and on change scores after intervention. Dependent t-tests were used to compare performance and change scores. RESULTS: The two approaches to rating both have moderate correlations (all data: 0.764; baseline: 0.677; post-intervention: 0.725) and yielded some different results in capturing performance. There was a significant difference in scores at pre-intervention between the two approaches to rating, even though post-intervention score mean difference was not significantly different. The PQRS-I had a wider score range, capturing wider performance differences, and greater change between baseline and post-intervention performances for children and young people with dystonic movement. CONCLUSIONS: Best practice in rehabilitation requires the use of outcome measures that optimally captures performance and performance change for children and young people with dystonic movement. When working with clients with severe motor-performance deficits, PQRS-I appears to be the better approach to capturing performance and performance changes.

Risk factors for symptomatic HIV-associated neurocognitive disorder in adults aged 50 and over attending a HIV clinic in Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorder (HAND), although prevalent, remains a poorly researched cause of morbidity particularly in sub-Saharan Africa (SSA). We aimed to explore the risk factors for HAND in people aged 50 and over under regular follow-up at a government HIV clinic in Tanzania. METHODS: HIV-positive adults aged 50 years and over were approached for recruitment at a routine HIV clinic appointment over a 4-month period. A diagnostic assessment for HAND was implemented, including a full medical/neurological assessment and a collateral history from a relative. We investigated potential risk factors using a structured questionnaire and by examination of clinic records. RESULTS: Of the cohort (n = 253), 183 (72.3%) were female and the median age was 57 years. Fifty-five individuals (21.7%) met the criteria for symptomatic HAND. Participants were at a greater risk of having symptomatic HAND if they lived alone [odds ratio (OR) = 2.566, P = .015], were illiterate (OR 3.171, P = .003) or older at the time of HIV diagnosis (OR = 1.057, P = .015). Age was correlated with symptomatic HAND in univariate, but not multivariate analysis. CONCLUSIONS: In this setting, HIV-specific factors, such as nadir CD4 count, were not related to symptomatic HAND. The "legacy theory" of early central nervous system damage prior to initiation of anti-retroviral therapy initiation may contribute, only in part, to a multifactorial aetiology of HAND in older people. Social isolation and illiteracy were associated with symptomatic HAND, suggesting greater cognitive reserve might be protective.

Screening for Instrumental Activities of Daily Living in Sub-Saharan Africa: A Balance Between Task Shifting, Simplicity, Brevity, and Training.

BACKGROUND: Task shifting has been suggested as one way to help manage the increasing burden of dementia in sub-Saharan Africa (SSA). However, brief, easy-to-use and valid screening tools are needed to support this approach. Our team has developed an 11-item questionnaire to assess instrumental activities of daily living (IADLs) in SSA, the Identification and Intervention for Dementia in Elderly Africans (IDEA)-IADL questionnaire. We aimed to externally validate the questionnaire and develop a shorter, more efficient version. METHODS: A community-based sample of 329 older adults in 4 rural villages was screened for dementia using the validated IDEA cognitive screen and the 11-item IDEA-IADL questionnaire. A stratified sample was assessed for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) dementia by a United Kingdom-based doctor, who was blinded to the results of screening. Area under the receiver operating characteristic (AUROC) curve analysis was used to assess validity, and factor analysis and regression modeling were used to develop a shorter version of the questionnaire. RESULTS: A 3-item IDEA-IADL questionnaire was developed and externally validated in the study sample. The questionnaire was deemed to be valid and enhanced screening performance in 2 villages (AUROC: 0.857 and 0.895) but detracted from the accuracy of the IDEA cognitive screen in the other 2 villages (AUROC: 0.591 and 0.639). These differences appeared to be due to differences in interpretation of responses to questions by the assessors. CONCLUSIONS: A brief IDEA-IADLs scale was developed and worked well in some villages. However, our study highlights a training need if brief screening tools to assess IADLs are to be effectively used by nonspecialists in low-resource settings.